An animal model in which the constituent parts of resistance and susceptibility to viral infection can be manipulated has been developed in this laboratory. It comprises congenic mice which are genetically resistant or susceptible to mouse hepatitis virus, and a pair of cloned virus derivatives, one of which has avirulent, the other virulent, characteristics when injected into the resistant strain of mice. The in vivo effect in mice is reflected in the in vitro behavior of macrophages from the respective hosts. This system can be modified phenotypically by rendering the susceptible mice or macrophages resistant by treatment with Concanavalin A or complete Freund's adjuvant. Conversely, the resistant mice or macrophages are rendered susceptible by treatment with cortisone and other reagents. These changes are probably mediated by the production of lymphokines by T lymphocytes. Funds are sought to determine: 1) the subsets and characteristics of T cells involved in production of the mediating lymphokines; 2) the in vitro susceptibility of the T cells from genetically susceptible, genetically resistant, and phenotypically modified mice to the wild type virus; 3) the relative efficacy of each of the 3 known reagents (cortisone, mixed lymphocyte culture, and seastar factor) which confers susceptibility on resistant cells - presumably via lymphocyte factors -on macrophages; relative duration of the effects, and the mechanism by which the effect is produced by each reagent; 4) whether the early pathological changes in the lymphocyte/macrophage system in the mouse are comparable to the in vitro changes.